tbuckley/cabot-search huggingface dataset:
Abstract 15289: Association Between Liver Stiffness and Prevalence of Stroke: Analysis of the National Health and Nutrition Examination Survey 2017 - 2020
Authors: Chawin Lopimpisuth, Pakin Lalitnithi, Chanattha Thimphitthaya, Watsachon Pangkanon, Chalothorn Wannaphut, Phuuwadith Wattanachayakul, Ekamol Tantisattamo
Journal: Circulation (2022)

Introduction: While cirrhotic patients increase risk of hemorrhagic and thrombotic events, association of liver stiffness with stroke remaines unclear. Hypothesis: Severity of liver stiffness is associated with higher prevalence of stroke. Methods: A cross-sectional study using the National Health and Nutrition Examination Survey (NHANES) 2017 to March 2020 included adult participants aged 21 to 79 years. Association between prevalence of self-reported stroke and liver stiffness stratified for 4 fibrosis scores measured by Fibroscan ™ were analyzed by multivariate logistic regression. Results: A total of 8,416 patients with Fibroscan results were identified (mean age 49 + 16 years old; 52% female; 32% white). Overall, 377 patients (4.5%) had a stroke. The number of participants stratified by 4 fibrotic stages of mild (F0F1), moderate (F2), severe fibrosis (F3), and cirhosis (F4) were 6,243 (74.2%), 826 (9.8%), 122 (1.4%), and 155 (1.8%) patients, respectively. In multivariate logistic regression, after controlling for age, race, gender, diabetic status, body mass index (&lt;25 vs &gt; 25 kg/m 2 ), and high systolic blood pressure ( &lt; 130 vs &gt;130 mmHg), individuals with severe fibrotic liver (F3 and F4) were significantly more likely to have a stroke (adjusted odds ratio (OR) 1.64; p= 0.044; 95% confidence interval (CI) 1.01, 2.65; Figure 1). Furthermore, we found that patients with cirrhosis (F4) were the most at risk to have a stroke (adjusted OR 1.91; p= 0.037; 95% CI 1.04, 3.49; Figure 1). Conclusions: In this cross-sectional data, there is a graded association between severe fibrotic liver disease measured by Fibroscan ™ and elevated prevalence of stroke. Longitudinal studies including additional risk factors of stroke such as hyperlipidemia, hypertension and atrial fibrillation need to be further evaluated.
Abstract 13942: Circular RNA-HIPK3 Suppresses Aortic Valve Calcification by Dual Inhibition of the Wnt/β-catenin Pathway in Aortic Valve Interstitial Cells
Authors: Gaopeng Xian, Rong Huang, Zeng Jingxin, Hengli Zhao, Su Shuwen, Shunyi Li, Dingli Xu, Qingchun Zeng
Journal: Circulation (2022)

Introduction: Calcific aortic valve disease (CAVD) has become an increasingly important worldwide medical problem without effective pharmacological intervention. Circular RNAs (circRNAs), a large class of non-coding RNAs, have been shown to play a critical role in the occurrence and progression of cardiovascular disease. However, the role of circRNAs in CAVD remains unclear. Methods and Results: High-throughput sequencing of circRNAs expression profiles in human calcified aortic valves and normal controls revealed that circRNA-HIPK3 (circHIPK3) was abundant in aortic valves but decreased in calcified aortic valves. Infecting the CAVD mouse model with adeno-associated virus subtype 9 expressing circHIPK3 (AAV9-circHIPK3) revealed that circHIPK3 overexpression reduced thickness and calcium deposition of the aortic valve leaflet in vivo . Gain- or loss-of-function experiments showed that circHIPK3 inhibited osteogenic responses in human aortic valve interstitial cells. MeRIP and RIP experiments showed that circHIPK3 enhanced the stability of suppressor of morphogenesis in genitalia 1 (SMG1) mRNA in an N6-methyladenosine (m 6 A)-dependent manner. Meanwhile, RNA pull-down and ChIP-Seq indicated that circHIPK3 increased the transcriptional activity of Chibby family member 1(CBY1) by promoting TATA-box binding protein-associated factor 15 (TAF15) intranuclear translocation. Furthermore, SMG1 and CBY1 negatively regulated the activity of Wnt/β-catenin pathway, and rescue experiments showed that circHIPK3 inhibited the Wnt/β-catenin pathway through increasing the expression of SMG1 and CBY1. Conclusions: Deficiency of circHIPK3 results in activation of the Wnt/β-catenin pathway and thereby induces aortic valve calcification. Exogenous circHIPK3 supplementation shows the ability to inhibit aortic valve thickening and calcification in vivo . Therefore, targeting circHIPK3 may be a potential strategy to prevent the development of CAVD.
Abstract 14295: Asymptomatic Frequent Atrial Ectopy in Healthy Children and Adolescents
Authors: Thomas Joyce, James J Joyce, Marye J Gleva, Sunita J Ferns
Journal: Circulation (2022)

Introduction: Premature atrial complexes (PACs) in pediatric patients with a structurally normal heart are usually presumed to be benign and self-resolving. On the contrary, adults with frequent PACs are at increased risk of multiple cardiovascular conditions. This study aims to evaluate a group of asymptomatic pediatric subjects with frequent PACs over time. Hypothesis: We hypothesized that, while most pediatric patients with frequent APCs have a benign prognosis there may be a subset that could progress to supraventricular arrhythmias Methods: Records for 343 pediatric patients (1-21 yrs) with asymptomatic frequent premature atrial complexes (&gt;50/24 hours) were selected from 6902 pediatric patients that underwent Holters over a 10 year period. Demographics, pertinent clinical characteristics and results of cardiac investigations were tabulated. Comparisons were made between Holter results at presentation and follow-up. Patients were classified into two groups on follow-up, those with a significant (&gt;20%) reduction in burden of atrial ectopy versus those with an insignificant (&lt;20%) reduction or increase in burden of atrial ectopy. Results: The median age at initial Holter was 8.26 (1.3-20.9) years with a comparable male to female ratio. An irregular heart rate was the most common reason for a Holter. The most common preexisting medical condition was attention deficit disorder, followed by asthma. Follow-up Holters were performed on 188(54.8%) patients at a median of 2.2 (0.5-8) yrs after the first Holter. Overall there was a significant decrease in atrial ectopy burden on repeat Holter examinations; median 3.6% (0.03-18.7) to 0.5% (0-19) with 166 (88.3%) patients demonstrating a decrease in atrial ectopy by over 20% of baseline. Ten (5.3%) patients had an increase in the ectopy burden over time and 12(6.3%) had an insignificant change. Non sustained supraventricular tachycardia was noted in three patients on the initial Holter but none on subsequent evaluations. Multivariate analysis identified a higher initial burden of PACs as a strong independent predictor for reduction in burden of ectopy with time (p&lt;0.005). Conclusions: Asymptomatic childhood PACs in the setting of a structurally normal heart are rare and tend to resolve with time.
Abstract 13913: Payer-Negotiated Prices for Transthoracic Echocardiography
Authors: Chen Wei, Michael Milligan, Ali A Assi, Miranda Lam, Alexander T Sandhu
Journal: Circulation (2022)

Introduction: Transthoracic echocardiography (TTE) is widely used in clinical practice. Medicare pays over $900 million annually for TTE. Using hospital-reported data, we sought to characterize variation in payer-negotiated (commercial) and self-pay prices for TTE within and across hospitals in the US. Methods: As of January 2021, federal price transparency legislation began requiring hospitals to publish chargemaster, discounted self-pay and commercial prices for all hospital services. We used the Turquoise Health database to gather this price data for TTE based on common procedural terminology (CPT) code 93306. Results: A total of 1,949 hospitals nationwide reported commercial prices for CPT 93306. Raw median prices varied widely across the US [$1398 (IQR $1064-$1661)] (Figure A). The median number of commercial plans per hospital was 20 (IQR 8-42) (Figure B). Compared with a median Medicare price of $464 (IQR $445-$493), the median commercial and discounted self-pay prices were $1313 (IQR $744-$1948) and $1422 (IQR $836-$2189) respectively, representing a 2.83- and 3.06-fold markup from the Medicare rate. The median chargemaster price was $2497 (IQR $1731-$3576), corresponding to a 5.38-fold markup. Within hospitals, the 90th percentile payer-negotiated rate was 2.78 (IQR 1.80-5.09) times the 10th percentile price (within-center ratio). Across hospitals within the same hospital referral region (HRR), the median price at the 90th percentile hospital was 2.47 (IQR 1.69-3.75) times that at the 10th percentile hospital (across-center ratio). Conclusions: Self-pay and commercial TTE prices are substantially higher than Medicare prices. There is significant variation in payer-negotiated rates within and across hospitals. More research is needed to understand the factors leading to this price variation and its relation to quality of care and access amidst rising healthcare costs in the US.
Abstract 13810: Development and Validation of the Peripheral Artery Questionnaire for Critical Limb Ischemia-(PAQ-CLI) Instrument
Authors: Kim G Smolderen, John Spertus, Gaelle Romain, Christina Pacheco, Kate Scott, Nancy Stone, Lindsey Scierka, Christine Fuss, Evy van Roij, Carlos Mena-Hurtado
Journal: Circulation (2022)

Background: Patients with critical limb ischemia (CLI) experience pain, non-healing wounds, and amputation, which impacts their health status. There are no CLI-specific health status instruments that meet FDA standards. We sought to develop and validate a CLI-specific health status instrument to supplement the Peripheral Artery Questionnaire (PAQ). Methods: Using the PAQ conceptual framework, the PAQ-CLI was created in 3 phases: (1) construct validity was established through qualitative input from patients and vascular specialists; (2) items were elicited for CLI clinical phenotypes (rest pain; wound; post-amputation) and tested with cognitive interviewing; (3) psychometric testing in the prospective SCOPE-CLI registry was completed to confirm factor structure, convergent validity (against the EQ-5D, maximum walking distance, and Wifi), internal consistency, and 1-month test-retest reliability (against 46 stable patients determined by global assessment of functioning change). Results: The original domain structure of the PAQ captured the full range of health status experiences, including physical function, symptom stability, symptoms, treatment satisfaction, quality of life, and social limitations, confirmed by eigenvalues &gt;1.77. After item-reduction (30 items for all clinical phenotype modules combined), the correlation with the PAQ-CLI summary score, EQ-5D Index, maximum walking distance, and Wifi wound and Ischemia score was 0.67, 0.38, -0.23 and -0.28, respectively. Cronbach’s alphas ranged from 0.85-0.88 and one-month test-retest reliability for the summary score was r=0.67. Baseline PAQ-CLI summary scores were lowest for rest pain (39.7±17.2), followed by wounds (49.0± 20.2), and highest for post amputation status (52.2±21.4) ( Figure) . Conclusion: The PAQ-CLI is a novel, validated instrument for patients with CLI meeting quality benchmarks for instrument development as defined by classical test theory.
Abstract 14287: Development of an Innovated Heart Failure Hospitalist Program Drives Best Practice and Exceptional Outcomes From 2018-2021
Authors: Jesus Vargas
Journal: Circulation (2022)

Introduction: Heart Failure (HF) is an important health care issue given its high prevalence, mortality, and cost of care. Despite numerous evidence-based strategies in the literature aiming at reducing HF readmissions, patients with HF remain at high risk for subsequent hospitalization with 20 to 25% readmitted within 30 days. Hypothesis: The UPMC Hospitalist and Cardiology leadership recognized the need to foster consistent inpatient hospitalist providers, which was lacking in the current model. The concept of a dedicated Heart Failure Hospitalist service line emerged. Methods: Patients with both primary HF: UPMC Hospitalist, Cardiologist, teaching service N= 4192 (70%); CHF hospitalist Team N=1785 (30%). Heart failure order set usage, length of stay, all-cause 30-day readmission rates, readmission with HF, cost per case were assessed between these two groups from 2018-2021. Results: All-cause 30-day HF readmission rates at UPMC (Harrisburg, West Shore, Community General Hospitals) for all providers is 21% from 2018-2021, matching the national average. HF Hospitalist team (only at Harrisburg Hospital) has consistently lower readmission rates: 9% (2018), 8.34% (2019), 8.6% (2020), 6.95% (2021). HF hospitalist length of stay was also consistently lower, by 0.5 to 0.9 days. Potential cost savings to UPMC hospitals is $1.5 million dollars since start of HF Hospitalist service line. Conclusions: Heart failure is a major health care issue. The HF Hospitalist service line was created to support an environment of patient-centered care by providing continuity of care for HF admissions and HF patients admitted for non-HF medical issues. The HF Hospitalists provide quality care with frequent daily rounding, optimization of HF medications, providing education to the patient and family to improve treatment plan adherence, as well as engaging in early discussion of palliative and hospice transition. At this community-based healthcare system, HF Hospitalist outcomes include decreasing length of stay; decreased 30 day all-cause readmission to an impressive 8.2%, and reduced 30 day HF readmissions 4.12%. This was done while reducing healthcare costs during the 4yrs of the HF Hospitalist service line at UPMC.
Abstract 13076: A Rare Stopgain Variant in <i>SLC25A2</i> Associates With Low Nitric Oxide and Poor Clinical Outcome in Hypoplastic Left Heart Syndrome
Authors: Wenjuan Zhu, Xinxiu Xu, Jiuann-huey I Lin, Phillip S Adams, Cecilia W Lo
Journal: Circulation (2022)

Introduction: Mitochondrial respiration defects accompanied by low nitric oxide (NO) are associated with heart failure in congenital heart disease (CHD) patients with hypoplastic left heart syndrome (HLHS). Here we investigated the genetic etiology of low NO in patients with CHD. Hypothesis: Mutations in mitochondrial-related genes involved in NO metabolism contributes to the low NO associated risk for heart failure and need for heart transplantation in HLHS. Methods and Results: We performed a case-control association study among 588 white CHD cases including 41 with HLHS, and 24,143 white controls from the genome aggregation database (gnomAD). A rare conserved stopgain variant (rs562886845) in SLC25A2 encoding mitochondrial ornithine transporter was significantly enriched among the HLHS patients with poor clinical outcome (Group II, Table 1), with 15.8% carrying this mutation, yielding odds ratio of 17.07 ( p = 5.23 х 10 -4 ) in comparison to CHD patients without left ventricular outflow tract obstruction or 7.63 ( p =2.68 х 10 –3 ) in comparison to gnomAD control cohort. Significantly, SLC25A2 is the only mitochondrial transporter exporting asymmetric dimethylarginine, a natural NO synthase inhibitor. The three HLHS patients with this SLC25A2 variant showed very low nasal NO (nNO), a proxy for endogenous NO production capacity. All three patients had received heart transplant, with two being heterozygous and one homozygous for this variant. Significantly, the HLHS patient with the homozygous mutation had nNO at background levels (2.8 nl/min at 7 years of age as compared to &gt;200 nl/min expected nNO). Conclusions: Our findings uncovered an essential role for SLC25A2 in determining NO production capacity in patients with HLHS. As all three HLHS patients with this variant and very low nNO survived with heart transplant, this variant should be further investigated as a genetic marker for predicting the need for early heart transplant in HLHS.
Abstract 12982: Between a Rock and a Hard Place: Stiff Left Atrial Syndrome in a Patient With Hereditary Rickets
Authors: Jonathan N Hourmozdi, Ruben Mylvaganam, Nausheen Akhter
Journal: Circulation (2022)

Introduction: Stiff left atrial syndrome (SLAS) is an uncommon cause of pulmonary hypertension (PH) that has been described as a complication of ablation for atrial fibrillation; here we describe a unique case of SLAS in the setting of extensive left atrial calcification from the treatment of hereditary hypophosphatemia (HH). Case Presentation: A 44-year-old woman with a history of HH presented for evaluation of progressive exertional dyspnea. Previous treatment with calcitriol and phosphate had been complicated by severe calcific mitral and aortic stenosis requiring aortic and mitral valve replacement eight years prior. She reported initial improvement in her symptoms after surgery, but more recently had noted worsening dyspnea and edema despite escalating her home diuretic dose. TTE was notable for moderately severe PH with no evidence of valvular or ventricular dysfunction. Chest CT showed extensive left atrial mural calcification (Figure A) with corresponding calcium visible in the wall of the left atrium on TTE (Figure B). The patient was admitted and underwent IV diuresis followed by RHC confirming mPAP of 41mmHg with a PCWP of 20mmHg and prominent V waves to 33mmHg (Figure C-D). PCWP was confirmed by wedge oxyhemoglobin saturation. Symptoms were improved but not resolved with additional diuresis. Discussion: In this patient with metastatic calcinosis related to the treatment of her HH, we believe her PH is most likely secondary to SLAS due to marked circumferential left atrial calcification. SLAS is characterized by decreased left atrial compliance, leading to large V waves in the absence of mitral regurgitation or an elevated LVEDP. Beyond diuresis, there are no proven treatments for PH due to SLAS.
Abstract 12877: Investigation of the Role of Fgf23 in the Pathogenesis of Post-Splenectomy Cardiovascular Dysfunction
Authors: Ling Wang, Taiju Satoh, Derek Sinchar, Timothy Bachman, Minying Yang, jeffrey J Baust, Mark T Gladwin, Hongshuai Li
Journal: Circulation (2022)

Introduction: Splenectomy is a relatively common surgical procedure in hematologic disorders, such as thalassemia, to improve anemia. However, splenectomy is clinically indicated as a strong risk factor for the development of post-splenectomy cardiovascular dysfunction. The underlying mechanisms have not been well established. We have found elevated levels of circulating FGF23 in thalassemia mice. As a hormone mainly expressed by osteocytes in bone, FGF23 has been shown to be an independent marker for cardiovascular risk in various patient populations. In this study we sought to investigate the role of FGF23 in the pathogenesis of post-splenectomy cardiovascular dysfunction. Methods: Splenectomy was performed in thalassemia ( Hbb th-3 ) mice at 4 weeks of age and cardiovascular functions were evaluated at 10 weeks post-splenectomy. Right ventricular maximum systolic pressure (RVSP) was measured using a closed chest right heart catheterization approach. Cardiac structure and functions were evaluated using echocardiography. Realtime RT-PCR and immunostaining were used to determine FGF23 expression in mouse tissues. Hepatocyte specific FGF23 KO thalassemia mice were generated by cross breeding albumin-Cre, Flox-Fgf23 and thalassemia mice. Results: Using a thalassemia mouse model ( Hbb th-3 ), we found that Hbb th-3 mice with surgical splenectomy developed significant cardiovascular dysfunction including biventricular cardiac hypertrophy, impaired diastolic function as well as pulmonary hypertension. We also found circulating levels of intact FGF23 were dramatically elevated in splenectomised Hbb th-3 mice, along with significantly upregulated FGF23 expression in liver and bone tissues. However, FGF23 levels in plasma were not normalized in hepatocyte specific FGF23 KO mice, suggesting bone-derived FGF23 is most likely the major source account for elevated FGF23 in circulation. Conclusions: Our findings suggest bone-derived FGF23 may contribute to the development of post-splenectomy cardiovascular dysfunction in thalassemia. The role of FGF23 in post-splenectomy pathogenesis will be further investigated using global FGF23 KO and osteocyte specific FGF23 KO mouse models.
Abstract 14759: Combining High-Sensitivity Cardiac Troponin and Donor-Derived Cell-Free Dna to Diagnose Acute Heart Transplant Rejection, on Behalf of the Graft Investigators
Authors: Palak Shah, Sean Agbor-Enoh, Scott Bruce, James A De Lemos, Erick McNair, Shashank Sinha, Hyesik Kong, Lawrence Henry, Inna Tchoukina, Keyur B Shah, Samer S Najjar, Steven Hsu, Maria E Rodrigo, Moon K Jang, Charles Marboe, Gerald J Berry, Mark Drazner, Hannah Valantine, Christopher Defilippi
Journal: Circulation (2022)

Introduction: Donor-derived cell-free DNA (%ddcfDNA) is a reliable non-invasive biomarker of acute rejection (AR). High-sensitivity cardiac troponin T (hs-cTnT) has been shown to be an easy to perform, low-cost, biomarker of myocyte injury. Hypothesis: We hypothesized that hs-cTnT correlates with %ddcfDNA in heart transplant patients and complements %ddcfDNA to improve the non-invasive diagnosis of AR. Methods: The Genomic Research Alliance for Transplantation (GRAfT) is a multicenter, prospective, longitudinal cohort study of heart transplant patients transplanted between 2015 and 2021. The %ddcfDNA was quantitated with shotgun sequencing; hs-cTnT was measured on the Roche instrument. AR was ISHLT grade ≥2R acute cellular rejection (ACR) or pAMR ≥1 antibody-mediated rejection (AMR). Results: This analysis included 171 patients from the GRAfT cohort (mean age 52.3±12.4 yrs; 41% Black; 31% Female). Of the 1,030 simultaneous measurements of hs-cTnT and %ddcfDNA, 662 were paired with an endomyocardial biopsy. Median hs-cTnT was 1451 ng/L (IQR: 865-1931) on post-operative day 1 and decayed to 26 ng/L (IQR: 18-56) at approximately 90-days. The Spearman correlation between %ddcfDNA and hs-cTnT was ρ=0.52 (p&lt;0.001). After 28 days, AR occurred in in 22% of patients (26 ACR and 17 AMR episodes). From day 28 on, %ddcfDNA and hs-cTnT detected AR with an area under the curve (AUC) of 0.88 (95%CI:0.84-0.92) and 0.74 (95%CI:0.63-0.84), respectively. When both biomarkers were combined, the AUC improved to 0.91 (95% CI:0.86-0.96, Figure). Conclusions: %ddcfDNA and hs-cTnT correlate moderately after heart transplant. Performance of hs-cTnT at diagnosing AR was inferior to %dd-cfDNA. When both biomarkers were combined, the overall diagnostic performance improved beyond that provided by %ddcfDNA alone.